Inhibition of the complement membrane attack complex by the galactose-specific adhesion of Entamoeba histolytica.

Braga, Lúcia Libanez Bessa Campelo; Ninomiya, Hirokazu; McCoy, James; Eacker, Stephen; Wiedmer, Therese; Pham, Christine; Wood, Sheila; Sims, P.; Petri, William A.

doi:10.1172/jci115931

Cited by 179 publications

(93 citation statements)

References 22 publications

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“…Since cathelicidin killing relies on disruption of the integrity of microbial membranes (24), the composition of the surface membrane of E. histolytica likely determines this innate resistance to cathelicidins. The membrane of E. histolytica trophozoites contains galactose/N-acetyl galactosamine-inhibitable lectin (Gal/ GalNac-lectin), lipophosphoglycan (LPG), and lipophosphopeptidogyclan (LPPG) (22), which participate in adhesion and induction of a proinflammatory response but may also protect from the lytic action of proteins such as cathelicidins or complement components (2,23). Another strategy of resistance could involve the highly charged LPPG glycoconjugates of E. histolytica (22), which might neutralize cationic defensins by altering the cell surface charge, like the anionic capsule polysaccharides of Pseudomonas aeruginosa and Escherichia coli (18).…”

Section: Figmentioning

confidence: 99%

Entamoeba histolytica Induces Intestinal Cathelicidins but Is Resistant to Cathelicidin-Mediated Killing

Cobo

Hirata

et al. 2012

Infect Immun

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The enteric protozoan parasite Entamoeba histolytica is the cause of potentially fatal amebic colitis and liver abscesses. E. histolytica trophozoites colonize the colon, where they induce inflammation, penetrate the mucosa, and disrupt the host immune system. The early establishment of E. histolytica in the colon occurs in the presence of antimicrobial human (LL-37) and murine (CRAMP [cathelin-related antimicrobial peptide]) cathelicidins, essential components of the mammalian innate defense system in the intestine. Studying this early step in the pathogenesis of amebic colitis, we demonstrate that E. histolytica trophozoites or their released proteinases, including cysteine proteinase 1 (EhCP1), induce intestinal cathelicidins in human intestinal epithelial cell lines and in a mouse model of amebic colitis. Despite induction, E. histolytica trophozoites were found to be resistant to killing by these antimicrobial peptides, and LL-37 and CRAMP were rapidly cleaved by released amebic cysteine proteases. The cathelicidin fragments however, did maintain their antimicrobial activity against bacteria. Degradation of intestinal cathelicidins is a novel function of E. histolytica cysteine proteinases in the evasion of the innate immune system in the bowel. Thus, early intestinal epithelial colonization of invasive trophozoites involves a complex interplay in which the ultimate outcome of infection depends in part on the balance between degradation of cathelicidins by amebic released cysteine proteinases and upregulation of proinflammatory mediators which trigger the inflammatory response.T he organism Entamoeba histolytica is a protozoan parasite that causes amebic colitis and liver abscesses through water-and food-borne infection. Approximately 10% of the world's population is infected with Entamoeba, and it is a major cause of death from parasitic infections (29). Colonization of the intestinal tract by E. histolytica follows binding of the amebic surface Gal/GalNAc adherence lectin to epithelial mucin oligosaccharides, with subsequent degradation of the mucin polymer network, extracellular matrix proteins, and components of the innate host defense by released cysteine proteinases (17,20,21,27,28). This early establishment of E. histolytica triggers an inflammatory response, which plays a role in the ultimate outcome of infection (4, 13).Cathelicidins are small cationic antimicrobial peptides of the mammalian innate immune system with broad activity against bacteria (6,10,11,15) and protozoa (7,9,19). LL-37 is the only cathelicidin described in humans (8) and CRAMP (cathelinrelated antimicrobial peptide) is the cathelicidin found in mice (6). Both LL-37 and CRAMP have related structure, function, and distribution in epithelial cells, including the intestine of humans and mice, and are part of the defense against microbial epithelial infections (32). For example, expression of LL-37 mRNA and protein was increased by Helicobacter pylori in gastric epithelial cells (11), and CRAMP protected mice from colonic colonizati...

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Section: Figmentioning

confidence: 99%

Entamoeba histolytica Induces Intestinal Cathelicidins but Is Resistant to Cathelicidin-Mediated Killing

Cobo

Hirata

et al. 2012

Infect Immun

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“…Braga et al en 1992, demostraron la similitud entre la lectina de adherencia y la proteína CD59 de las células sanguíneas, por lo que la E. histolytica evade la lisis inducida por complemento 21,22 . Kassai et al (1988) propusieron unificar la terminología para denominar las enfermedades parasitarias, para dejar el nombre de amebiosis al agregar el sufijo -osis; sin embargo, en la actualidad sólo la aceptan los médicos veterinarios y no los parasitólogos humanos 23,24 .…”

Section: This Article Presents a History Of Entamoeba Histolytica Spaunclassified

Historia del protozoo Entamoeba histolytica

2008

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“…Other infectious agents, like B. burgdorferi, have been reported to constitutively express on their outer membrane molecules that show molecular mimicry and functional similarity with CD59. This group includes viruses, such as herpesvirus saimiri (47), or parasites, like Entamoeba histolytica (48), and Schistosoma mansoni (49), the latter expressing a 94-kDa protein at some stages of development, such as schistosomula and lung and adult worms.…”

Section: Figurementioning

confidence: 99%

Serum-Resistant Strains of Borrelia burgdorferi Evade Complement-Mediated Killing by Expressing a CD59-Like Complement Inhibitory Molecule

Pausa¹,

Pellis²,

Cinco

et al. 2003

The Journal of Immunology

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Borrelia burgdorferi, the etiological agent of Lyme disease, comprises three genospecies, Borrelia garinii, afzelii, and burgdorferi sensu strictu, that exhibit different pathogenicity and differ in the susceptibility to C-mediated killing. We examined C-sensitive and C-resistant strains of B. burgdorferi for deposition of C3 and late C components by fluorescence microscope and flow cytometry. Despite comparable deposition of C3 on the two strains, the resistant strain exhibited reduced staining for C6 and C7, barely detectable C9, and undetectable poly C9. Based on these findings, we searched for a protein that inhibits assembly of C membrane attack complex and documented an anti-human CD59-reactive molecule on the surface of C-resistant spirochetes by flow cytometry and electron microscopy. A molecule of 80 kDa recognized by polyclonal and monoclonal anti-CD59 Abs was identified in the membrane extract of C-resistant strains by SDS-PAGE and Western blot analysis. The molecule was released from the bacterial wall using deoxycholate and trypsin, suggesting its insertion into the bacterial membrane. The CD59-like molecule acts as C inhibitor on Borrelia because incubation with F(ab′)2 anti-CD59 renders the serum-resistant strain exquisitely susceptible to C-mediated killing and guinea pig erythrocytes bearing C5b-8, unlike the RBC coated with C5b-7, are protected from reactive lysis by the bacterial extract. Western blot analysis revealed preferential binding of the C inhibitory molecule to C9 and weak interaction with C8β.

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Inhibition of the complement membrane attack complex by the galactose-specific adhesion of Entamoeba histolytica.

Cited by 179 publications

References 22 publications

Entamoeba histolytica Induces Intestinal Cathelicidins but Is Resistant to Cathelicidin-Mediated Killing

Entamoeba histolytica Induces Intestinal Cathelicidins but Is Resistant to Cathelicidin-Mediated Killing

Historia del protozoo Entamoeba histolytica

Serum-Resistant Strains of Borrelia burgdorferi Evade Complement-Mediated Killing by Expressing a CD59-Like Complement Inhibitory Molecule

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